Thalidomide and Birth Defects

Fraga, Lucas Rosa; Diamond, Alexandra J.; Vargesson, Neil

doi:10.1002/9780470015902.a0026052

Cited by 3 publications

(2 citation statements)

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“…The science that studies the CAs caused by these teratogens and how they affect the embryo by studying pathways and mechanisms that could be caused or altered by them is known as teratology ("teratos" = monster, "logos" = study; Ujházy et al, 2012). A teratogen can be any factor that is extrinsic to embryonic development, such as recreational drugs, medications, biological agents, x-rays and maternal conditions (Brent, 2001;Fraga et al, 2016;Vargesson and Fraga, 2017;Moore et al, 2019). Alcohol, cocaine and nicotine are examples of recreational drugs that are teratogenic (Cambell, 2003;Williams et al, 2015;Holbrook, 2016).…”

Section: Congenital Anomalies and Teratogenesis-a Reviewmentioning

confidence: 99%

From the Farm to the Lab: How Chicken Embryos Contribute to the Field of Teratology

et al. 2021

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Congenital anomalies and its causes, particularly, by external factors are the aim of the field called teratology. The external factors studied by teratology are known as teratogens and can be biological or environmental factors for example, chemicals, medications, recreational drugs, environmental pollutants, physical agents (e.g., X-rays and maternal hyperthermia) and maternal metabolic conditions. Proving the teratogenicity of a factor is a difficult task requiring epidemiology studies as well as experimental teratology evidence from the use of animal models, one of which is the chicken embryo. This model in particular has the advantage of being able to follow development live and in vivo, with rapid development hatching around 21 days, is cheap and easy to manipulate and to observe development. All this allows the chicken embryo to be used in drug screening studies, teratogenic evaluation and studies of mechanisms of teratogenicity. The chicken embryo shares morphological, biochemical and genetic similarities with humans as well as mammalian species, making them ideal to ascertain the actions of teratogens, as well as screen drugs to test for their safety. Pre-clinical trials for new drugs are carried out in rodents and rabbits, however, chicken embryos have been used to screen new compounds or analogs of thalidomide as well as to investigate how some drugs can lead to congenital malformations. Indeed, the chicken embryo has proved valuable in understanding how many congenital anomalies, seen in humans, arise following teratogen exposure. The aim of this review is to highlight the role of the chicken embryo as an experimental model for studies in teratology, exploring its use in drug screening studies, phenotypic evaluation and studies of teratogenic mechanisms of action. Here, we discuss many known teratogens, that have been evaluated using the chicken embryo model including some medicines, such as, thalidomide, valproic acid; recreational drugs including alcohol; environmental influences, such as viruses, specifically ZIKV, which is a newly discovered human teratogen. In addition, we discuss how the chicken embryo has provided insight on the mechanisms of teratogenesis of many compounds and also how this impact on drug safety.

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Section: Congenital Anomalies and Teratogenesis-a Reviewmentioning

confidence: 99%

From the Farm to the Lab: How Chicken Embryos Contribute to the Field of Teratology

et al. 2021

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“…Functionalized isoindole-1,3-dione derivatives exhibit a vast range of biological activities 1 such as antibacterial, 2 teratogenic, 3 anticancer (multiple myeloma), 4 PPAR- agonist, 5 and anti-inflammatory activities. 6 Bioactive molecules containing an isoindol-1-3-dione moiety include Thalidomide 1, Pomalidomide 2, and Apremilast 3 (Figure 1).…”

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Click Chemistry Approach to Isoindole-1,3-dione Tethered 1,2,3-Triazole Derivatives

Kaur

Singh

Kumar

et al. 2019

SynOpen

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The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos

Brown

Fraga

Cameron

et al. 2018

Sci Rep

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Primodos was a hormone pregnancy test used between 1958–1978 that has been implicated with causing a range of birth defects ever since. Though Primodos is no longer used, it’s components, Norethisterone acetate and Ethinyl estradiol, are used in other medications today including treatments for endometriosis and contraceptives. However, whether Primodos caused birth defects or not remains controversial, and has been little investigated. Here we used the developing zebrafish embryo, a human cell-line and mouse retinal explants to investigate the actions of the components of Primodos upon embryonic and tissue development. We show that Norethisterone acetate and Ethinyl estradiol cause embryonic damage in a dose and time responsive manner. The damage occurs rapidly after drug exposure, affecting multiple organ systems. Moreover, we found that the Norethisterone acetate and Ethinyl estradiol mixture can affect nerve outgrowth and blood vessel patterning directly and accumulates in the forming embryo for at least 24 hrs. These data demonstrate that Norethisterone acetate and Ethinyl estradiol are potentially teratogenic, depending on dose and embryonic stage of development in the zebrafish. Further work in mammalian model species are now required to build on these findings and determine if placental embryos also are affected by synthetic sex hormones and their mechanisms of action.

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Thalidomide and Birth Defects

Cited by 3 publications

References 61 publications

From the Farm to the Lab: How Chicken Embryos Contribute to the Field of Teratology

From the Farm to the Lab: How Chicken Embryos Contribute to the Field of Teratology

Click Chemistry Approach to Isoindole-1,3-dione Tethered 1,2,3-Triazole Derivatives

The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos

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